Prolonged high glucose suppresses phorbol 12-myristate 13-acetate and ionomycin-induced interleukin-2 mRNA expression in Jurkat cells

• Published in: Biochimica et Biophysica Acta (BBA) - General Subjects Vol. 1790; no. 1; pp. 8 - 15
• Main Authors: Higai, Koji, Tsukada, Masatoshi, Moriya, Yumiko, Azuma, Yutaro, Matsumoto, Kojiro
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2009; Elsevier BV
• Subjects: Cyclic AMP Response Element Modulator; Cyclic AMP Response Element Modulator - biosynthesis; Cyclic AMP Response Element Modulator - genetics; Glucose; Glucose - pharmacology; Glucose - physiology; High concentration of glucose; Humans; Inducible cAMP early repressor; Interleukin-2; Interleukin-2 - antagonists & inhibitors; Interleukin-2 - biosynthesis; Interleukin-2 - genetics; Ionomycin; Ionomycin - pharmacology; Jurkat Cells; NFATC Transcription Factors; NFATC Transcription Factors - genetics; Nuclear factor of activated T cells; Promoter Regions, Genetic; RNA, Messenger; RNA, Messenger - antagonists & inhibitors; RNA, Messenger - biosynthesis; Tetradecanoylphorbol Acetate; Tetradecanoylphorbol Acetate - pharmacology; Time Factors; Transcription Factor AP-1; Transcription Factor AP-1 - genetics; High concentration of glucose; Interleukin-2; Inducible cAMP early repressor; Nuclear factor of activated T cells
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2008.10.002

The disturbance of immunological responses is a complication of diabetes mellitus. We cultured Jurkat cells in 11.1 (normal) and 22.2 mmol/l (high) glucose for 12 weeks and stimulated them with 10 nmol/l phorbol 12-myristate 13-acetate (PMA) and 500 nmol/l ionomycin. RT-PCR revealed that induced interleukin (IL)-2 mRNA expression levels were suppressed in high glucose cultures compared to those in normal glucose. Promoter activities of IL-2, nuclear factor of activated T cells (NFAT), and activator protein-1 (AP-1), after 6 h stimulation with PMA and ionomycin, gradually decreased in high glucose cultures to approximately 20% of those in normal glucose at 12 weeks. The prolonged culture in high glucose increased inducible cAMP early repressor (ICER) II mRNA and protein levels, and overexpression of ICER II dose-dependently suppressed promoter activities of IL-2, NFAT, and AP-1. Moreover, ICER II mRNA expression was transiently induced by stimulation with PMA and ionomycin in normal glucose cultures; however, with high glucose, the induction disappeared. These results indicate that ICER II protein accumulates during prolonged culture in high glucose and suppresses IL-2 mRNA expression in Jurkat cells.